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Page 4 of 8 Lo Re et al. J Cancer Metastasis Treat 2019;5:81 I http://dx.doi.org/10.20517/2394-4722.2019.30

A B C

D E

Figure 2. A: Hematologic outcome of population cells: decrease of platelets and lymphocytes count after therapy followed by stability
of count cells during physical activity. Stability over time of hemoglobin level and white blood cells types; B: lymphocyte subpopulation
during physical activity: progressive reduction of CD3, CD4 and CD8 followed by an increase, a wave trend of CD16 and stability of HLA-
DR and Treg cells; C: initial reduction of Platelet/lymphocyte ratio followed by stabilization during therapy; it is followed by initial slight
increase followed by stability and therefore slight reduction during exercise. Furthermore is shown a relative stability of neutrophil/
lymphocyte, CD4/Treg, CD8/Treg ratios; D: recovery of albumin levels and decrease of CRP after therapy followed by stability during
physical activity; E: decrease of Ca 19.9 after therapy followed by the stability over time together of CEA levels during exercise

It is known how the magnitude of the tumor mutation burden correlates with the probability of response to
the new checkpoint inhibitory agents that have recently entered clinical practice in the treatment of tumors.

PDAC is also negatively influenced by the low tumor mutation burden, characterized by low prevalence of
somatic mutations and of neo-antigens expression with consequent resistance to new immunotherapeutic
[13]
agents, such as anti-PD1 . One of the key points of immunosuppression also present in PDAC is
represented by the CXCR4/CXCL12 axis. In fact, from its block derives the promotion of intratumoral
lymphocyte infiltration and the synergism of action with anti-PD-1 agent .
[14]
Among the external factors, physical activity is very important in the homeostasis of the organism. It
exercises antitumor activity in animal models and high levels of post-diagnosis exercise reduce the risk of
[15]
recurrence and cancer-specific mortality in common solid tumors . Such exercise must be undertaken
gradually until a constant level is reached and maintained (inverted-J hypothesis), whereby regular
moderate exercise improves immune system function while acute, intermittent efforts correlate with
[16]
immunosuppression and increased susceptibility to cancer .
Regarding the repercussions of physical activity and immune surveillance, the cells that are most stimulated
are the natural killer (NK) cells, influenced by neuroendocrine [17,18] and immunological mechanism such as
[19]
IL-6 secretion resulting from muscle stress .

However, discordant results have been reported in animal and clinical studies and were reiterated in a
systematic literature review on the repercussions of physical exercise on NK cell counts and cytotoxicity.
Indeed, definitive conclusions cannot yet be drawn because of the diversity in the intensity and duration of
the exercise and in the time of blood sampling .
[20]